tbuckley/cabot-search huggingface dataset:
PB2283: COVID-19 (SARS-COV-2 INFECTION) IN LYMPHOMA PATIENTS
Authors: I. Tytorenko, I. Kryachоk, O. Alexik, T. Kadnikova, A. Martynchik, O. Novosad, Y. Pastyshenko, Y. Stepanishina, N. Shokun, K. Filonenko
Journal: HemaSphere (2022)

Background: Observations from initial case series suggested that cancer patients in general might have an unfavorable outcome following coronavirus disease 2019 (COVID-19), due to their underlying conditions and cytotoxic treatments. Lymphoma patients may be especially vulnerable, due to the immunodeficiency and immune dysregulation caused by the lymphoma itself and the antitumor treatments. Aims: analysis of the flow of coronavirus disease (COVID-19) in cases of the patients with non-Hodgkin’s lymphoma and Hodgkin’s lymphoma on the background of specific treatment. Patients with lymphoma appear particularly vulnerable to SARS-CoV-2 infection, only partly because of the detrimental effects of the anti-neoplastic regimens (chemotherapy, pathway inhibitors, monoclonal antibodies) on the immune system. Methods: The National Cancer Institute conducted a retrospective analysis of the course of the disease on COVID-19 from March 2020 to October 2021. The study included 87 patients. The average age of the patients was 30.4 years (from 23 to 75 years old). 60 patients had non-Hodgkin’s lymphoma, 19 patients had Hodgkin’s lymphoma, and 8 had multiple myeloma. Results: Coronavirus disease in 85 % of the patients was confirmed by PCR, in 15% - by IFM (detected IgM). Severe cases of coronavirus disease were observed in 19.23 %, moderate severity - in 53.8% of the patients, light- in 26.9%. Covid-19 pneumonia was diagnosed in 74.71% of the patients. The duration of coronavirus disease ranged from 7 to 60 days, on average of 26.56 days, in cases of 22 patients (25.28 %) - more than 30 days. 18 patients (20.68%) died due to complications of coronavirus disease. Fatalities were more common among patients with DBCL - 29.16 %, and among patients with recurrent and refractory forms of the disease - 33.33 %. The type of anticancer therapy affected the outcome of the disease, mortality was more common among patients receiving chemotherapy RB and RdaEPOCH regimens, respectively 31.57 % and 40%. Among of toxicity after continued special treatment in 11.5 % patients were recorded complications - pulmonitis, 8 patients with thromboembolic complications, 1 patient developed pulmonary embolism. Patients after infection before the start of special treatment required a recovery period, which averaged 21.7 days, ranging from 7 to 60 days. Summary/Conclusion: COVID-19 infection is of particular concern for morbidity and mortality of patients with lymphoma due to their immunodeficiency status and 11.5% caused by the disease itself and / or its treatment. Patients with lymphoproliferative diseases are more likely to have moderate COVID-19 disease, mortality from complications is higher than in cases of the population and makes up 20.68%.
Delayed-onset bleeding after transrectal prostate biopsy presenting as a rectal Dieulafoy’s lesion
Authors: Mitsunobu Saito, Gota Sudo, Hiroyuki Inoue, Yumemi Takada, Katsuyoshi Miura, Atsushi Yawata, Hiroshi Nakase
Journal: Endoscopy (2022)

Rectal bleeding is a well-known adverse event related to transrectal prostate biopsy, with a frequency ranging from 0 % to 37 % [1]. Most bleeding is mild and resolves with conservative management. Severe bleeding, affecting up to 1 % of patients undergoing transrectal prostate biopsy, is uncommon but can be life-threatening [2]. Rectal bleeding typically occurs immediately after the biopsy. Delayed-onset bleeding is rare although several cases have been reported [3] [4]. Herein, we present a case of delayed-onset severe bleeding after transrectal prostate biopsy, which was successfully treated with endoscopic clipping ([Video 1]).
Socioeconomic Deprivation: An Important, Largely Unrecognized Risk Factor in Primary Prevention of Cardiovascular Disease
Authors: Dorien M. Kimenai, Leah Pirondini, John Gregson, David Prieto, Stuart J. Pocock, Pablo Perel, Tilly Hamilton, Paul Welsh, Archie Campbell, David J. Porteous, Caroline Hayward, Naveed Sattar, Nicholas L. Mills, Anoop S.V. Shah
Journal: Circulation (2022)

Socioeconomic deprivation is associated with higher cardiovascular morbidity and mortality. Whether deprivation status should be incorporated in more cardiovascular risk estimation scores remains unclear. This study evaluates how socioeconomic deprivation status affects the performance of 3 primary prevention cardiovascular risk scores.The Generation Scotland Scottish Family Health Study was used to evaluate the performance of 3 cardiovascular risk scores with (ASSIGN [Assessing cardiovascular risk using SIGN (Scottish Intercollegiate Guidelines Network) guidelines to ASSIGN preventive treatment]) and without (SCORE2 [Systematic Coronary Risk Evaluation 2 algorithm], Pooled Cohort Equations) socioeconomic deprivation as a covariate in the risk prediction model. Deprivation was defined by Scottish Index of Multiple Deprivation score. The predicted 10-year risk was evaluated against the observed event rate for the cardiovascular outcome of each risk score. The comparison was made across 3 groups defined by the deprivation index score consisting of group 1 defined as most deprived, group 3 defined as least deprived, and group 2, which consisted of individuals in the middle deprivation categories.The study population consisted of 15 506 individuals (60.0% female, median age of 51). Across the population, 1808 (12%) individuals were assigned to group 1 (most deprived), 8119 (52%) to group 2, and 4708 (30%) to group 3 (least deprived), and 871 (6%) individuals had a missing deprivation score. Risk scores based on models that did not include deprivation status significantly under predicted risk in the most deprived (6.43% observed versus 4.63% predicted for SCORE2 [P=0.001] and 6.69% observed versus 4.66% predicted for Pooled Cohort Equations [P<0.001]). Both risk scores also significantly overpredicted the risk in the least deprived group (3.97% observed versus 4.72% predicted for SCORE2 [P=0.007] and 4.22% observed versus 4.85% predicted for Pooled Cohort Equations [P=0.028]). In contrast, no significant difference was demonstrated in the observed versus predicted risk when using the ASSIGN risk score, which included socioeconomic deprivation status in the risk model.Socioeconomic status is a largely unrecognized risk factor in primary prevention of cardiovascular disease. Risk scores that exclude socioeconomic deprivation as a covariate under- and overestimate the risk in the most and least deprived individuals, respectively. This study highlights the importance of incorporating socioeconomic deprivation status in risk estimation systems to ultimately reduce inequalities in health care provision for cardiovascular disease.
Chronic myeloid leukemia: 2022 update on diagnosis, therapy, and monitoring
Authors: Elias Jabbour, Hagop Kantarjian
Journal: American Journal of Hematology (2022)

Abstract Disease Overview Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm with an incidence of 1–2 cases per 100 000 adults. It accounts for approximately 15% of newly diagnosed cases of leukemia in adults. Diagnosis CML is characterized by a balanced genetic translocation, t (9;22) (q34;q11.2), involving a fusion of the Abelson gene ( ABL1 ) from chromosome 9q34 with the breakpoint cluster region ( BCR ) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a BCR::ABL1 fusion oncogene, which in turn translates into a BCR::ABL1 oncoprotein. Frontline Therapy Four tyrosine kinase inhibitors (TKIs), imatinib, dasatinib, bosutinib, and nilotinib are approved by the United States Food and Drug Administration for first‐line treatment of newly diagnosed CML in chronic phase (CML‐CP). Clinical trials with second generation TKIs reported significantly deeper and faster responses but had no impact on survival prolongation, likely because of the availability of effective TKIs salvage therapies for patients who have a cytogenetic relapse with frontline TKI therapy. Salvage Therapy For CML post failure on frontline therapy, second‐line options include second and third generation TKIs. Although potent and selective, these TKIs exhibit unique pharmacological profiles and response patterns relative to different patient and disease characteristics, such as patients' comorbidities, disease stage, and BCR::ABL1 mutational status. Patients who develop the T315I “gatekeeper” mutation display resistance to all currently available TKIs except ponatinib, asciminib, and olverembatinib. Allogeneic stem cell transplantation remains an important therapeutic option for patients with CML‐CP and failure (due to resistance) of at least two TKIs, and for all patients in advanced phase disease. Older patients who have a cytogenetic relapse post failure on all TKIs can maintain long‐term survival if they continue a daily most effective/least toxic TKI, with or without the addition of non‐TKI anti‐CML agents (hydroxyurea, omacetaxine, azacitidine, decitabine, cytarabine, busulfan and others).
Interactions among the mycobiome, bacteriome, inflammation, and diet in people living with HIV
Authors: María José Gosalbes, Nuria Jimenéz-Hernandéz, Elena Moreno, Alejandro Artacho, Xavier Pons, Sonia Ruíz-Pérez, Beatriz Navia, Vicente Estrada, Mónica Manzano, Alba Talavera-Rodriguez, Nadia Madrid, Alejandro Vallejo, Laura Luna, José A. Pérez-Molina, Santiago Moreno, Sergio Serrano-Villar
Journal: Gut Microbes (2022)

While the intestinal microbiome seems a major driver of persistent immune defects in people with HIV (PWH), little is known about its fungal component, the mycobiome. We assessed the inter-kingdom mycobiome–bacteriome interactions, the impact of diet, and the association with the innate and adaptive immunity in PWH on antiretroviral therapy. We included 24 PWH individuals and 12 healthy controls. We sequenced the Internal Transcribed Spacer 2 amplicons, determined amplicon sequence variants, measured biomarkers of the innate and adaptive immunity in blood and relations with diet. Compared to healthy controls, PWH subjects exhibited a distinct and richer mycobiome and an enrichment for Debaryomyces hansenii, Candida albicans, and Candida parapsilosis. In PWH, Candida and Pichia species were strongly correlated with several bacterial genera, including Faecalibacterium genus. Regarding the links between the mycobiome and systemic immunology, we found a positive correlation between Candida species and the levels of proinflammatory cytokines (sTNF-R2 and IL-17), interleukin 22 (a cytokine implicated in the regulation of mucosal immunity), and CD8+ T cell counts. This suggests an important role of the yeasts in systemic innate and adaptive immune responses. Finally, we identified inter-kingdom interactions implicated in fiber degradation, short-chain fatty acid production, and lipid metabolism, and an effect of vegetable and fiber intake on the mycobiome. Therefore, despite the great differences in abundance and diversity between the bacterial and fungal communities of the gut, we defined the changes associated with HIV, determined several different inter-kingdom associations, and found links between the mycobiome, nutrient metabolism, and systemic immunity.
GPRC5D-Directed CAR Yields 100% Response Rate
Journal: Cancer Discovery (2022)

Patients with refractory or relapsed multiple myeloma usually develop resistance to the two approved BCMA-targeting chimeric antigen receptor (CAR) T cells. A preliminary study of a new CAR T-cell therapy that zeroes in on the GPRC5D protein on multiple myeloma cells suggests that this approach is safe and effective. All 10 patients treated with the GPRC5D-targeting cells showed responses.
Inhibition of Karyopherin β1-Mediated Nuclear Import Disrupts Oncogenic Lineage-Defining Transcription Factor Activity in Small Cell Lung Cancer
Authors: Demetra P. Kelenis, Kathia E. Rodarte, Rahul K. Kollipara, Karine Pozo, Shreoshi Pal Choudhuri, Kyle B. Spainhower, Sarah J. Wait, Victor Stastny, Trudy G. Oliver, Jane E. Johnson
Journal: Cancer Research (2022)

Abstract Genomic studies support the classification of small cell lung cancer (SCLC) into subtypes based on the expression of lineage-defining transcription factors ASCL1 and NEUROD1, which together are expressed in ∼86% of SCLC. ASCL1 and NEUROD1 activate SCLC oncogene expression, drive distinct transcriptional programs, and maintain the in vitro growth and oncogenic properties of ASCL1 or NEUROD1-expressing SCLC. ASCL1 is also required for tumor formation in SCLC mouse models. A strategy to inhibit the activity of these oncogenic drivers may therefore provide both a targeted therapy for the predominant SCLC subtypes and a tool to investigate the underlying lineage plasticity of established SCLC tumors. However, there are no known agents that inhibit ASCL1 or NEUROD1 function. In this study, we identify a novel strategy to pharmacologically target ASCL1 and NEUROD1 activity in SCLC by exploiting the nuclear localization required for the function of these transcription factors. Karyopherin β1 (KPNB1) was identified as a nuclear import receptor for both ASCL1 and NEUROD1 in SCLC, and inhibition of KPNB1 led to impaired ASCL1 and NEUROD1 nuclear accumulation and transcriptional activity. Pharmacologic targeting of KPNB1 preferentially disrupted the growth of ASCL1+ and NEUROD1+ SCLC cells in vitro and suppressed ASCL1+ tumor growth in vivo, an effect mediated by a combination of impaired ASCL1 downstream target expression, cell-cycle activity, and proteostasis. These findings broaden the support for targeting nuclear transport as an anticancer therapeutic strategy and have implications for targeting lineage-transcription factors in tumors beyond SCLC. Significance: The identification of KPNB1 as a nuclear import receptor for lineage-defining transcription factors in SCLC reveals a viable therapeutic strategy for cancer treatment.
BRAF inhibitors in BRAFV600E-mutated pediatric high-grade gliomas: Upfront or at recurrence?
Authors: Liana Nobre, Eric Bouffet
Journal: Neuro-Oncology (2022)

Journal Article BRAF inhibitors in BRAFV600E-mutated pediatric high-grade gliomas: Upfront or at recurrence? Get access Liana Nobre, Liana Nobre Division of Hematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Eric Bouffet Eric Bouffet Division of Hematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada Corresponding Author: Eric Bouffet, MD, Division of Hematology/Oncology, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON M5G 1X8, Canada (eric.bouffet@sickkids.ca). https://orcid.org/0000-0002-6832-6539 Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 24, Issue 11, November 2022, Pages 1976–1977, https://doi.org/10.1093/neuonc/noac160 Published: 24 June 2022 Article history Published: 24 June 2022 Corrected and typeset: 07 July 2022
Complete closure of a large mucosal defect (100 mm) after gastric endoscopic submucosal dissection, using the "accordion fold" method
Authors: Yohei Ikenoyama, Masaki Katsurahara, Kyosuke Tanaka, Misaki Nakamura, Yasuhiko Hamada, Noriyuki Horiki, Hayato Nakagawa
Journal: Endoscopy (2022)

Closure of defects after gastric endoscopic submucosal dissection (ESD) can reduce the risk of complications [1]. Although various endoscopic closure methods are proposed, mainly for the duodenum and colon [2] [3] [4], closure of gastric mucosal defects is difficult because of the thick and hard wall [5], which is one reason why a standard closure method has not yet been established. We performed complete closure of an extremely large defect after gastric ESD using the "accordion fold" method, a combination of dental floss-assisted and mucosal–submucosal clipping ([Video 1]).
PB1793: NEUTROPHIL TO LYMPHOCYTE RATIO AS A PROGNOSTIC FACTOR IN AML AND MDS
Authors: V. Van Oorschot, M. Beckers
Journal: HemaSphere (2022)

Background: The neutrophil to lymphocyte ratio (NLR) reflects the balance between innate and adaptive immunity and has been studied as a prognostic biomarker in several solid and some hematological malignancies. In the tumor micro-environment, lymphocytes have an anti-tumor activity, while neutrophils possess a pro-tumor activity. Several studies show that a higher NLR is associated with an increased risk of mortality. Only a few studies are available on NLR in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Aims: The aim of this study is to investigate if the NLR can be a prognostic marker in AML and MDS. The effect of age and cytogenetic risk profile on NLR is also investigated. Methods: In this single-center, retrospective study 261 AML patients and 105 MDS patients treated at the University Hospitals of Leuven were included. The patients were divided into two subgroups by defining NLR=2.0 as the cut-off point. The NLR was calculated by the ratio of the amount of neutrophils to lymphocytes in the peripheral blood (PB). Further division was made based on treatment: stem cell transplant, hypomethylating agents or supportive therapy. Kaplan-Meier analyses were used to assess overall survival (OS). Survival predictors were analyzed using Cox regression with uni- and multivariate analyses. The correlation between age, cytogenetic risk profile and NLR was analyzed using independent-samples median tests. Results: AML patients with low NLR (<2.0) had a longer OS than those with high NLR (≥2.0). NLR, age, hemoglobin, neutrophil count, and lymphocyte count in PB had a significant effect on OS in all AML patients. NLR was no longer significant in multivariate analysis. Furthermore, a high NLR before receiving stem cell transplant was associated with longer OS. Regarding MDS, no significant difference in OS was found between patients with low (<2.0) and high NLR (≥2.0). Finally, in AML patients higher age was associated with an increase in NLR. Image:Summary/Conclusion: NLR at the time of diagnosis may be predictive for OS in AML patients but not in MDS patients. However our findings need to be confirmed in larger cohorts.
Aggregation‐Induced Emission (AIE) and Magnetic Resonance Imaging Characteristics for Targeted and Image‐Guided siRNA Therapy of Hepatocellular Carcinoma
Authors: Yu‐chen Hou, Chao Zhang, Zi‐jie Zhang, Lei Xia, Ke‐qiang Rao, Li‐hong Gu, Yi‐chi Wu, Zi‐cheng Lv, Hao‐xiang Wu, Xiao‐lei Zuo, Fan Li, Hao Feng, Qiang Xia
Journal: Advanced Healthcare Materials (2022)

Abstract Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and remains a global health challenge. Small interfering RNA (siRNA) is a promising therapeutic modality that blocks multiple disease‐causing genes without impairing cell structures. However, siRNA therapeutics still have off‐target proportion and lack effective quantitative analysis method in vivo. Thus, a novel theragnostic nanoparticle with dual‐mode imaging is synthesized for targeted and image‐guided siRNA therapy of HCC. Survivin siRNA is carried by Poly‐ethylenimine (PEI) and interacted with T7‐AIE/Gd NPs, which are self‐assembled of DSPE‐PEG‐DTPA(Gd), DSPE‐PEG‐Mal, DSPE‐PEG‐PEI, and TPE. The resulting theragnostic nanoparticles exhibit lower toxicity and high therapeutic effect, and excellent T1‐weighted magnetic resonance imaging (MRI) and aggregation‐induced emission (AIE) imaging performance. Moreover, in vivo MRI and AIE imaging indicate that this kind of theragnostic nanoparticles rapidly accumulates in the tumor due to active targeting and enhanced permeability and retention (EPR) effects. Sur@T7‐AIE‐Gd suppresses HCC tumor growth by inducing autophagy and destabilizes DNA integrity in tumor cells. The results suggest that T7‐AIE‐Gd nanoparticles carrying Survivin siRNA with dual‐mode imaging characteristics are promising for targeted and image‐guided siRNA therapy of hepatocellular carcinoma.
Underwater endoscopic mucosal resection for a protruding lesion in the esophagus
Authors: Paul Doumbe-Mandengue, Sophie Geyl, Anne Guyot, Mathieu Pioche, Rebecca Rodrigues, Jérémie Albouys, Jérémie Jacques
Journal: Endoscopy (2022)

A 70-year-old man with a history of ischemic cardiopathy, taking clopidogrel as his usual treatment, was referred because of cholangitis. Computed tomography and magnetic resonance imaging scans revealed a dilated bile duct without any obvious obstruction. Gastroscopy and endoscopic ultrasound were performed in search of an ampulloma, and unexpectedly identified a sessile tumor 2 cm above the gastroesophageal junction ([Fig. 1]). Gastroscopy performed with a high definition endoscope and magnification (EG-760Z; Fujifilm, Tokyo, Japan) confirmed a 0-Ip esophageal lesion with a suspicious irregular mucosal and vascular pattern ([Fig. 2]).
Intelligent cataract surgery supervision and evaluation via deep learning
Authors: Ting Wang, Jun Xia, Ruiyang Li, Ruixin Wang, Nick Stanojcic, Ji-Peng Olivia Li, Erping Long, Jinghui Wang, Xiayin Zhang, Jianbin Li, Xiaohang Wu, Zhenzhen Liu, Jingjing Chen, Hui Chen, Danyao Nie, Huanqi Ni, Ruoxi Chen, Wenben Chen, Shiyi Yin, Duru Lin, Pisong Yan, Zeyang Xia, Shengzhi Lin, Kai Huang, Haotian Lin
Journal: International Journal of Surgery (2022)
Endoscopic ultrasound-guided gastrojejunostomy and choledochoduodenostomy with lumen-apposing metal stents: an efficient approach to double endoscopic bypass
Authors: Abdulrahman Qatomah, Abrar Nawawi, Ali Bessissow, Jeffrey Barkun, Corey Miller, Yen-I Chen
Journal: Endoscopy (2022)

Concomitant malignant gastric outlet and biliary obstruction is a morbid complication of pancreatic cancer [1]. Double endoscopic bypass with endoscopic ultrasound-guided gastroenterostomy (EUS-GE) and an EUS-guided choledochoduodenostomy or hepatogastrostomy is a promising but technically challenging modality in gastric outlet and biliary obstruction [2]. The advent of dedicated biliary lumen-apposing metal stents (LAMS) [3] has the potential to greatly facilitate double endoscopic bypass and enhance its adoptability [2].
Fazirsiran for Liver Disease Associated with Alpha <sub>1</sub> -Antitrypsin Deficiency
Authors: Pavel Strnad, Mattias Mandorfer, Gourab Choudhury, William Griffiths, Christian Trautwein, Rohit Loomba, Thomas Schluep, Ting Chang, Min Yi, Bruce D Given, James C Hamilton, Javier San Martin, Jeffery H Teckman
Journal: New England Journal of Medicine (2022)

Alpha1-antitrypsin (AAT) deficiency results from carriage of a homozygous SERPINA1 "Z" mutation (proteinase inhibitor [PI] ZZ). The Z allele produces a mutant AAT protein called Z-AAT, which accumulates in hepatocytes and can lead to progressive liver disease and fibrosis. This open-label, phase 2 trial investigated the safety and efficacy of fazirsiran, an RNA interference therapeutic, in patients with liver disease associated with AAT deficiency.
First report of closure of an iatrogenic recto-vesical fistula solely using endoscopic negative pressure therapy
Authors: Gunnar Loske, Wolfgang Schulze, Ralf-Uwe Kiesow, Marcus Kurzidem, Salvador Fernandez de la Maza, Christian Theodor Müller
Journal: Endoscopy (2022)

A 70-year-old man presented with a recto-vesical fistula (rectal urinary leakage, pneumaturia, fecaluria). Four days earlier, he had injured himself during anal manipulation with a stick. Endoscopically and cystographically, a transmural perforation, 1.5 cm in diameter, and a fistula canal, 5 cm long, was found ([Video 1]).